Biyoinformatik araçlarla VDR geni ve ürününün karşılaştırmalı analizi

Abstract

Amaç: Bu çalışma, insan VDR molekülüne homolog protein dizileri, promotor dizileri üzerinde genel transkripsiyon faktör bağlanma yerleri, korunan bölgelerin filogenetik ilişkileri ve araştırılan ESTdb’lerin varlığında EST verilerine bağlı ekspresyon profilleri gibi genin ve onun ürünlerinin özelliklerini araştırmak amacı ile planlandı. Gereç-Yöntem: Biz, farklı anlı türlerinde biyoinformatik araçları kullanarak ESTdb’den EST verilerine dayanarak VDR genin homolojisini, korunan bölgelerini, promotor ve ekspresyon profillerini inceledik. Sonuçlar: Bu çalışmanın sonuçları, VDR molekülünün çalışılan tüm organizmalar arasında, örneğin Macaca mulatta 98% , Saguinus oedipus 98% ve Petromyzon marinus 59% ’un insana benzediğini ve orta derecede korunduğunu gösterdi. ZnF_C4 nükleer hormon reseptöründe C4 çinko ucu ve HOLI hormonların ligand bağlama alanı alanlarına göre bir kaç benzer motif belirlendi. Ayrıca insanın normal ve kanserli dokuları arasında gen ekspresyonu bakımından anlamlı fark olduğu gösterildi. Yorum: Bu çalışma, farklı canlı türlerinde VDR gen promotoru üzerinde herhangi bir genel transkripsiyon bağlama yerinin olmadığını kanıtladı. Yakınlık metodu NJ ’na dayanarak oluşturulan filogenetik ağaçlar, ZnF_C4 ve HOLI dizilerinin yakın evrimsel ilişkisini gösterdi

Keywords

• VDR,Biyoinformatik,Karşılaştırmalı genomik,in silico Biyoloji

Computational analysis of VDR gene and its product using Bioinformatics tools

Abstract

Background: The aims of this study was to analyze some properties of this gene and its products; such as the homologous protein sequences to human VDR molecule, the common transcription factor binding sites on promoter sequences, phylogenetic relationships of the conserved domains, and in silico expression profiles based on EST data that presence in ESTdb in all investigated. Methods: We investigated the homology, conserved domain, promoter and expression profiles of the VDR gene based on EST data from the ESTdb by using bioinformatics tools in different species. Results: The results of this study indicated that VDR molecule is middling conserved among all studied organisms; for example, human similar to Macaca mulatta 98% and Saguinus oedipus 98% , to Petromyzon marinus 59% . From the point of view of ZnF_C4 C4 zinc finger in nuclear hormone receptors and HOLI Ligand binding domain of hormones domains, it was obtained several similar motifs. Separately, it was seen that there was significantly difference gene expression in normal and cancer tissues of brain in human. Conclusion: This study demonstrated that there was no common transcription factor binding sites in promoter VDR gene in different species. Phylogenetic trees constructed using the neighbor-joining method NJ revealed a close evolutionary relationship of ZnF_C4 and HOLI in various species

Keywords

• VDR,Bioinformatics,Comparative genomics,in silico Biology

References

1. elements. The Baker AR, McDonnell DP, Hughes M, et al. Cloning and expression of full-length cDNA encoding Human vitamin D receptor. Proc Nat Acad Sci. 1988; 85:3294-3298.
2. Faraco JH, Morrison NA, Baker A, Shine J, Frossard PM. ApaI dimorphism at the human Vitamin D receptor gene locus. Nucleic Acids Res. 1989; 17:2150.
3. Szpirer J, Szpirer C, Riviere M, et al. The Sp1 transcription factor gene (SP1) and the 1, 25-dihydroxyvitamin D (3) Receptor gene (VDR) are colocalized on human chromosome arm 12q and rat chromosome 7. Genomics. 1991; 11:168-173.
4. Labuda M, Fujiwara TM, Ross MV, et al. Two hereditary defects related to vitamin D metabolism map to the same region of human chromosome 12q13-14. J Bone Miner Res. ; 7:1447-1453. Miyamoto K
5. Yamamoto H, et al. Structural organization of the human vitamin D Receptor chromosomal gene and its promoter. Molec Endocr. 1997; :1165-1179. Kesterson RA
6. Makishima M, Lu TT, Xie W, et al. Vitamin D receptor as an intestinal bile acid sensor. Science. 2002; 296:1313-1316.
7. Kamei Y, Kawada T, Fukuwatari T, et al. Cloning and sequence of the gene encoding the mouse vitamin D receptor. Gene. 1995; :281-282.
8. Jurutka PW, Remus LS, Whitfield GK, et al. The polymorphic N terminus in human vitamin D receptor isoforms influences transcriptional interaction with transcription factor IIB. Molec Endocr. 2000; 14:401-420. by modulating

9. Fang Y, van Meurs JBJ, d'Alesio A, et al. Promoter and 3-prime-untranslated-region haplotypes in the vitamin D receptor gene predispose to osteoporotic fracture: the Rotterdam Study. Am J Hum Genet. 2005; :807-823.
10. MB. Cloning and Characterization of the Vitamin D Receptor from Xenopus laevis. Endocrinology. 1997; 138:2347-2353. of nuclearreceptors: a perspective from structural genomics. Structure. 2003; 11:741
11. Schuetz EG. Evolutionary selection across the nuclear hormone receptor superfamily with a focus on the NR1I subfamily (vitamin D, pregnane X, and constitutive androstane receptors). Nuclear Receptor. 2005; 3:1-20.
12. EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990; 215:403-410.
13. AA, et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Research. 1997; :3389-3402. al. CLUSTALW: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994; 22:4673-4680.
14. Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment. Brief Bioinf. 2004; 5:150-163.
15. Corresponding Author: Fuat DILMEC, Harran University, Medicine Faculty, Department of Medical Biology Sanliurfa-Turkey Tel: [phone] 06 Fax: [phone] E-mail: [e-mail] expression analysis of query genes based on ESTs. Bioinformatics. 2003; 19:653-654.
16. Prostate derived ETS transcription factor shows better tumor-association than other cancer-associated reports. 2004; 11:453-458. hormone receptor superfamily. Science. 1988; :889-895. of gene expression by the thyroid hormone receptor. Biochim Biophys. Acta. 1990; :157-176. receptors in differentiation, embryo-genesis, and neoplasia. FASEB J. 1991; 5:2924-2933.
17. Transcriptional regulation by the nuclear receptor superfamily. Curr Opin Biotechnol. ; 3:597-602. Structure-Function Analysis of Vitamin D and VDR Model. Current Pharmaceutical Design. ; 6:733-748. et al. SAGEmap: a public gene expression resource. Genome Res. 2000; 10:1051-60.
18. B, et al. GATA-4 and MEF2C transcription factors control the tissue specific expression of the alphaT-catenin gene CTNNA3. Nucleic Acids Res. 2004; 32:4155-4165. Oncology
19. Evans RM. The steroid and thyroid Glass CK, Holloway JM. Regulation De Luca LM . Retinoids and their Yu VC, Naar AM, Rosenfield MG. Yamada S, Yamamoto K, Masuno H. Lash AE, Tolstoshev CM, Wagner L, Vanpoucke G, Goossens S, De Craene Doan LL, Porter SD, Duan Z, et al. Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells. Nucleic Acids Res. 2004; 32:2508-2519.
20. MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics. 2005; 21:2933-2942. Isolation dihydroxyvitamin D receptor cDNA. Proc Natl Acad of rat ,25- Sci USA. ; :1005-1009